A dual role for GABA in quasi-morphine abstinence behavior induced by di-n-propylacetate involving both initiation and termination.
Di-n-propylacetate (DPA) induces a behavioral syndrome in rats resembling morphine abstinence behavior. The inhibitory action of DPA on GABA degradation, resulting in an enhanced release of GABA, is probably responsible for this behavioral effect, since GABA antagonists, like bicuculline and picrotoxin, have been shown to suppress this behavior. However, the time-course of the DPA-induced behavior is much shorter than that of the DPA-induced increase of GABA concentrations. Therefore, we have studied the influence of enhanced GABA levels caused by a first injection of DPA and the behavior evoked by a second injection of DPA at different time intervals after the first injection. The results indicate that GABA fulfills a role in both the initiation and termination of DPA-induced behavior. The mechanism responsible for this dual action of GABA is ascribed to a differential sensitivity to DPA of the nerve terminal and glial metabolic compartments of GABA in the brain. The increase of GABA in the nerve terminal caused by DPA is probably responsible for the initiation of the quasi-abstinence behavior, whereas the overflow of GABA into the synaptic cleft may be responsible for the suppression of this behavior via stimulation of presynaptic autoreceptors. Another mechanism responsible for the rapid termination of the DPA-evoked behavior could be the formation of DPA metabolites which antagonize this behavior. From the results of experiments using some primary metabolites of DPA, a role for these metabolites in the termination of the DPA-induced behavior seems unlikely.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004361:Drug Tolerance; D006801:Humans; D006900:Hydroxylation; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid